SUMMARY: Developmental Dyslexia (DD) is a strongly heritable specific learning disability of neurobiological origin, but the underlying neural mechanisms are largely unknown. Although DD is not diagnosed until a child has failed to learn to read, usually in late elementary school, after reading impairments and associated psychological burdens manifest, interventions are most effective in younger children. Thus, to date, DD is generally diagnosed after the most effective time for intervention has passed. A tentative pathway between genetic effects, early brain development, and behavior in DD has been proposed but only a few studies have examined longitudinal brain development in infants at risk for DD and none have investigated the development of brain structure or metabolic function. Furthermore, although behavioral research has demonstrated a strong relationship between reading skills in parents and their children, the intergenerational transmission of structural and functional brain alterations in DD is unknown. Building on our previous work, which showed atypical functional and structural brain development in infants, preschoolers, and kindergarteners at-risk for dyslexia, the goal of this proposed project is to characterize trajectories of early brain development in infants with (FHD+) and without (FHD-) a familial risk for DD from early infancy through elementary school and to further examine intergenerational transmission of brain alterations associated with DD in child-parent dyads. We will utilize a longitudinal approach and MR measures will be obtained in a new infant cohort, and an existing child cohort for which infant data have already been collected. Furthermore, the parents of all children will be examined. Using functional and structural magnetic resonance imaging as well as magnetic resonance spectroscopy and behavioral measures, Aim 1 (cross-sectional) will characterize atypical structural, functional and metabolic brain development in FHD+ compared to FHD- infants and children at 5 time points. Aim 2 (longitudinal) utilizes growth curve and trajectory analyses to characterize and compare developmental trajectories of FHD+ and FHD- infants from infancy through elementary school. Aim 3 will examine the intergenerational transmission of brain structure/function critical for reading as well as behavioral reading skills in children-parent dyads. The current practice of DD diagnosis only after years of reading failure is detrimental to the well-being of children and their families who experience the psychosocial implications of DD for years prior to diagnosis. Identifying the underlying neural mechanisms of DD in infancy is highly innovative and has the potential to inform early identification of children at risk and the development of early preventive and intervention strategies during a period of heightened brain plasticity. It may also draw increased research attention to this age group (infancy) in DD and has the potential to provide a model for longitudinal studies of other developmental disabilities. It can further highlight the importance of examining brain development trajectories starting in infancy to illuminate emerging brain-behavior associations across the developmental timeline.